Mutation spectrum and birth prevalence of inborn errors of metabolism among Emiratis. A study from Tawam hospital metabolic center, United Arab Emirates

This study aimed to determine the mutation spectrum and prevalence of inborn errors of metabolism [IEM] among Emiratis. The reported mutation spectrum included all patients who were diagnosed with IEM [excluding those with lysosomal storage diseases [LSD]] at Tawam Hospital Metabolic Center in Abu Dhabi, United Arab Emirates, between January 1995 and May 2013. Disease prevalence [per 100,000 live births] was estimated from data available for 1995-2011. In 189 patients, 57 distinct IEM were diagnosed, of which 20 [35%] entities were previously reported LSD [65 patients with 39 mutations], with a birth prevalence of 26.87/100,000. This study investigated the remaining 37 [65%] patients with other IEM [124 patients with 62 mutations]. Mutation analysis was performed on 108 [87%] of the 124 patients. Five patients with biotinidase deficiency had compound heterozygous mutations, and two siblings with lysinuric protein intolerance had two homozygous mutations. The remaining 103 [95%] patients had homozygous mutations. As of this study, 29 [47%] of the mutations have been reported only in Emiratis. Two mutations were found in three tribes [biotinidase deficiency [BTD, c.1330G>C] and phenylketonuria [PAH, c.168+5G>C]]. Two mutations were found in two tribes [isovaleric aciduria [IVD, c.1184G>A] and propionic aciduria [PCCB, c.990dupT]]. The remaining 58 [94%] mutations were each found in individual tribes. The prevalence was 48.37/100,000. The most prevalent diseases [2.2-4.9/100,000] were biotinidase deficiency; tyrosinemia type 1; phenylketonuria; propionic aciduria; glutaric aciduria type 1; glycogen storage disease type Ia, and mitochondrial deoxyribonucleic acid depletion. The IEM birth prevalence [LSD and non-LSD] was 75.24/100,000. These results justify implementing prevention programmes that incorporate genetic counselling and screening

New and known mutations associated with inborn errors of metabolism in a heterogeneous Middle Eastern population

To identify the mutations underlying a number of inborn errors of metabolism [IEM] disorders among United Arab Emirates [UAE] residents. Molecular diagnostic and bioinformatics tools were used to identify the causative mutations of IEM disorders from multi-ethnic patients residing in UAE. The study was conducted in Al-Ain, UAE, between April 2009 and September 2010. This is a case series retrospective study where patients attending the metabolic clinic at Tawam Hospital were recruited. Thirty patients and 26 parents were included. We present evidence in the UAE of 7 new mutations and 19 mutations that have previously been reported in other populations, all causing a number of common IEM disorders, including phenylketonuria, maple syrup urine disease, glycogen storage diseases, beta-ketothiolase deficiency, and Zellweger syndrome among many others. Reflecting the diverse ethnic groups residing in the UAE, we found mutations in several different population groups. However, consanguinity is evident in most cases. This report is of utmost importance for taking the necessary steps toward the prevention of inherited disorders, not just in the UAE, but anywhere in the world where these Arab and Asian populations reside, or where consanguinity is a cultural norm

novel mutation in ARG1 gene is responsible for arginase deficiency in an Asian family

Argininemia is a rare autosomal recessive metabolic disorder caused by a deficiency in the arginase enzyme, which is the final enzyme in the urea cycle and responsible for the hydrolysis of arginine to urea and ornithine. The disease becomes symptomatic during childhood and is characterized by progressive spastic quadriplegia, progressive mental impairment, growth retardation, and periodic episodes of hyperammonemia. At least 19 distinct mutations in the ARG1 gene have been identified indicating the molecular heterogeneity of this condition. We report a homozygous novel mutation [c.93 delG] in the ARG1 gene from 3 affected children of a Pakistani family living in the United Arab Emirates. The mutation is expected to lead to a frame shift after the thirtieth residue and a stop codon at residue 44 [p.T30fsX14]. Therefore, this mutation is expected to result in complete loss-of-function of the arginase enzyme and therefore is the mostly likely cause of argininemia in this family